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1.
J Zoo Wildl Med ; 55(3): 750-756, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39255218

ABSTRACT

Outbreaks of suspected tick-borne disease (redwater fever) have been reported in captive deer of the Scottish Highlands. In this pilot study, polymerase chain reaction and amplicon sequencing were used to detect tick-borne pathogens in opportunistically collected blood and spleen samples from 63 (healthy, n = 44; diseased, n = 19) cervids, and 45 questing and feeding ticks (Ixodes ricinus) from the outbreak sites in 2021-2022. Potentially pathogenic Babesia species were detected in deer but not identified in ticks, Anaplasma phagocytophilum was detected in both deer and ticks, and Borrelia afzelii was detected in ticks but not in deer. Sequencing confirmed Babesia capreoli and Babesia cf. odocoilei parasitemia in clinically healthy red deer (Cervus elaphus), B. capreoli parasitemia in clinically healthy domestic reindeer (Rangifer tarandus tarandus), and two cases of B. cf. odocoilei-associated hemolytic anemia in white-lipped deer (Cervus albirostris), of which one was fatal despite imidocarb treatment. White-lipped deer appear to be highly susceptible to babesiosis caused by B. cf. odocoilei. This investigation highlights the importance of disease surveillance, including molecular diagnostics, for the detection of emerging tick-borne pathogens in managed populations of cervids.


Subject(s)
Anaplasma phagocytophilum , Babesia , Babesiosis , Deer , Ehrlichiosis , Animals , Deer/parasitology , Babesia/isolation & purification , Anaplasma phagocytophilum/isolation & purification , Babesiosis/epidemiology , Babesiosis/parasitology , Ehrlichiosis/veterinary , Ehrlichiosis/epidemiology , Scotland/epidemiology , Female , Male , Ixodes/microbiology , Ixodes/parasitology
2.
Parasit Vectors ; 17(1): 380, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39238018

ABSTRACT

BACKGROUND: Ticks carry a variety of microorganisms, some of which are pathogenic to humans. The human risk of tick-borne diseases depends on, among others, the prevalence of pathogens in ticks biting humans. To follow-up on this prevalence over time, a Belgian study from 2017 was repeated in 2021. METHODS: During the tick season 2021, citizens were invited to have ticks removed from their skin, send them and fill in a short questionnaire on an existing citizen science platform for the notification of tick bites (TekenNet). Ticks were morphologically identified to species and life stage level and screened using multiplex qPCR targeting, among others, Borrelia burgdorferi (sensu lato), Anaplasma phagocytophilum, Borrelia miyamotoi, Neoehrlichia mikurensis, Babesia spp., Rickettsia helvetica and tick-borne encephalitis virus (TBEV). The same methodology as in 2017 was used. RESULTS: In 2021, the same tick species as in 2017 were identified in similar proportions; of 1094 ticks, 98.7% were Ixodes ricinus, 0.8% Ixodes hexagonus and 0.5% Dermacentor reticulatus. A total of 928 nymphs and adults could be screened for the presence of pathogens. Borrelia burgdorferi (s.l.) was detected in 9.9% (95% CI 8.2-12.0%), which is significantly lower than the prevalence of 13.9% (95% CI 12.2-15.7%) in 2017 (P = 0.004). The prevalences of A. phagocytophilum (4.7%; 95% CI 3.5-6.3%) and R. helvetica (13.3%; 95% CI 11.2-15.6%) in 2021 were significantly higher compared to 2017 (1.8%; 95% CI 1.3-2.7% and 6.8%; 95% CI 5.6-8.2% respectively) (P < 0.001 for both). For the other pathogens tested, no statistical differences compared to 2017 were found, with prevalences ranging between 1.5 and 2.9% in 2021. Rickettsia raoultii was again found in D. reticulatus ticks (n = 3/5 in 2021). Similar to 2017, no TBEV was detected in the ticks. Co-infections were found in 5.1% of ticks. When combining co-infection occurrence in 2017 and 2021, a positive correlation was observed between B. burgdorferi (s.l.) and N. mikurensis and B. burgdorferi (s.l.) and B. miyamotoi (P < 0.001 for both). CONCLUSIONS: Although the 2021 prevalences fell within expectations, differences were found compared to 2017. Further research to understand the explanations behind these differences is needed.


Subject(s)
Anaplasma phagocytophilum , Borrelia burgdorferi , Borrelia , Encephalitis Viruses, Tick-Borne , Ixodes , Animals , Belgium/epidemiology , Humans , Prevalence , Encephalitis Viruses, Tick-Borne/isolation & purification , Encephalitis Viruses, Tick-Borne/genetics , Borrelia/isolation & purification , Borrelia/genetics , Borrelia/classification , Ixodes/microbiology , Ixodes/virology , Borrelia burgdorferi/isolation & purification , Borrelia burgdorferi/genetics , Anaplasma phagocytophilum/isolation & purification , Anaplasma phagocytophilum/genetics , Babesia/isolation & purification , Babesia/genetics , Rickettsia/isolation & purification , Rickettsia/genetics , Rickettsia/classification , Female , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/microbiology , Tick-Borne Diseases/virology , Male , Dermacentor/microbiology , Dermacentor/virology , Nymph/microbiology , Nymph/virology , Ticks/microbiology , Ticks/virology , Tick Bites/epidemiology
3.
J Infect Dis ; 230(Supplement_1): S1-S10, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39140724

ABSTRACT

Lyme arthritis (LA) was recognized as a separate entity in 1975 because of geographic clustering of children often diagnosed with juvenile rheumatoid arthritis in Lyme, Connecticut. After identification of erythema migrans as a common early feature of the illness, a prospective study of such patients implicated Ixodes scapularis ticks in disease transmission. In 1982, the causative agent, now called Borrelia burgdorferi, was cultured from these ticks and from Lyme disease patients. Subsequently, it was shown that LA could usually be treated successfully with oral antibiotics but sometimes required intravenous antibiotics. Yet, a small percentage of patients developed a dysregulated, proinflammatory immune response leading to persistent postinfectious synovitis with vascular damage, cytotoxic and autoimmune responses, and fibroblast proliferation, a lesion similar to that of rheumatoid arthritis. The message from postinfectious LA for other autoimmune arthritides is that a complex immune response with autoimmune features can begin with a microbial infection.


Subject(s)
Lyme Disease , Lyme Disease/immunology , Humans , Animals , History, 20th Century , Borrelia burgdorferi/immunology , History, 21st Century , Anti-Bacterial Agents/therapeutic use , Ixodes/microbiology
4.
J Infect Dis ; 230(Supplement_1): S82-S86, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39140718

ABSTRACT

Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by Ixodes spp ticks. The rise in Lyme disease cases since its discovery in the 1970s has reinforced the need for a vaccine. A vaccine based on B burgdorferi outer surface protein A (OspA) was approved by the Food and Drug Administration (FDA) several decades ago, but was pulled from the market a few years later, reportedly due to poor sales, despite multiple organizations concluding that it was safe and effective. Newer OspA-based vaccines are being developed and are likely to be available in the coming years. More recently, there has been a push to develop vaccines that target the tick vector instead of the pathogen to inhibit tick feeding and thus prevent transmission of tick-borne pathogens to humans and wildlife reservoirs. This review outlines the history of Lyme disease vaccines and this movement to anti-tick vaccine approaches.


Subject(s)
Borrelia burgdorferi , Ixodes , Lyme Disease Vaccines , Lyme Disease , Lyme Disease/prevention & control , Lyme Disease/immunology , Humans , Animals , Borrelia burgdorferi/immunology , Lyme Disease Vaccines/immunology , Ixodes/microbiology , Vaccination , Bacterial Outer Membrane Proteins/immunology , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage , Antigens, Surface/immunology , Lipoproteins/immunology
5.
Front Cell Infect Microbiol ; 14: 1429667, 2024.
Article in English | MEDLINE | ID: mdl-39091677

ABSTRACT

Introduction: Tick-borne pathogens, such as Borreliella spp., Rickettsia spp., and Anaplasma spp., are frequently detected in Germany. They circulate between animals and tick vectors and can cause mild to severe diseases in humans. Knowledge about distribution and prevalence of these pathogens over time is important for risk assessment of human and animal health. Methods: Ixodes ricinus nymphs were collected at different locations in 2009/2010 and 2019 in Germany and analyzed for tick-borne pathogens by real-time PCR and sequencing. Results: Borreliella spp. were detected with a prevalence of 11.96% in 2009/2010 and 13.10% in 2019 with B. afzelii and B. garinii as dominant species. Borrelia miyamotoi was detected in seven ticks and in coinfection with B. afzelii or B. garinii. Rickettsia spp. showed a prevalence of 8.82% in 2009/2010 and 1.68% in 2019 with the exclusive detection of R. helvetica. The prevalence of Anaplasma spp. was 1.00% in 2009/2010 and 7.01% in 2019. A. phagocytophilum was detected in seven tick samples. None of the nymphs were positive for C. burnetii. Discussion: Here, observed changes in prevalence were not significant after a decade but require longitudinal observations including parameters like host species and density, climatic factors to improve our understanding of tick-borne diseases.


Subject(s)
Ixodes , Tick-Borne Diseases , Animals , Germany/epidemiology , Ixodes/microbiology , Prevalence , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/microbiology , Nymph/microbiology , Borrelia/isolation & purification , Borrelia/genetics , Humans , Rickettsia/genetics , Rickettsia/isolation & purification , Anaplasma/genetics , Anaplasma/isolation & purification , Real-Time Polymerase Chain Reaction
6.
Microb Genom ; 10(8)2024 Aug.
Article in English | MEDLINE | ID: mdl-39093316

ABSTRACT

Changing climates are allowing the geographic expansion of ticks and their animal hosts, increasing the risk of Borrelia-caused zoonoses in Canada. However, little is known about the genomic diversity of Borrelia from the west of the Canadian Rockies and from the tick vectors Ixodes pacificus, Ixodes auritulus and Ixodes angustus. Here, we report the whole-genome shotgun sequences of 51 Borrelia isolates from multiple tick species collected on a range of animal hosts between 1993 and 2016, located primarily in coastal British Columbia. The bacterial isolates represented three different species from the Lyme disease-causing Borrelia burgdorferi sensu lato genospecies complex [Borrelia burgdorferi sensu stricto (n=47), Borrelia americana (n=3) and Borrelia bissettiae (n=1)]. The traditional eight-gene multi-locus sequence typing (MLST) strategy was applied to facilitate comparisons across studies. This identified 13 known Borrelia sequence types (STs), established 6 new STs, and assigned 5 novel types to the nearest sequence types. B. burgdorferi s. s. isolates were further differentiated into ten ospC types, plus one novel ospC with less than 92 % nucleotide identity to all previously defined ospC types. The MLST types resampled over extended time periods belonged to previously described STs that are distributed across North America. The most geographically widespread ST, ST.12, was isolated from all three tick species. Conversely, new B. burgdorferi s. s. STs from Vancouver Island and the Vancouver region were only detected for short periods, revealing a surprising transience in space, time and host tick species, possibly due to displacement by longer-lived genotypes that expanded across North America.This article contains data hosted by Microreact.


Subject(s)
Borrelia , Genotype , Ixodes , Lyme Disease , Multilocus Sequence Typing , Phylogeny , Whole Genome Sequencing , Animals , Whole Genome Sequencing/methods , Borrelia/genetics , Borrelia/classification , Borrelia/isolation & purification , Canada , Ixodes/microbiology , Lyme Disease/microbiology , British Columbia , Genome, Bacterial , Ticks/microbiology
7.
J Infect Dis ; 230(Supplement_1): S18-S26, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39140719

ABSTRACT

Lyme disease is a zoonotic infection due to Ixodes tick-transmitted Borrelia burgdorferi sensu lato spirochetes and the most common vector-borne disease in the Northern Hemisphere. Despite nearly 50 years of investigation, the pathogenesis of this infection and its 2 main adverse outcomes-postinfectious Lyme arthritis and posttreatment Lyme disease syndrome-are incompletely understood. Advancement in sequencing and mass spectrometry have led to the rapid expansion of high-throughput omics technologies, including transcriptomics, metabolomics, and proteomics, which are now being applied to human diseases. This review summarizes findings of omics studies conducted on blood and tissue samples of people with acute Lyme disease and its postinfectious outcomes.


Subject(s)
Lyme Disease , Metabolomics , Proteomics , Humans , Lyme Disease/microbiology , Animals , Borrelia burgdorferi/genetics , Genomics , Ixodes/microbiology
8.
Parasit Vectors ; 17(1): 339, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39135071

ABSTRACT

BACKGROUND: Lyme disease continues to expand in Canada and the USA and no single intervention is likely to curb the epidemic. METHODS: We propose a platform to quantitatively assess the effectiveness of a subset of Ixodes scapularis tick management approaches. The platform allows us to assess the impact of different control treatments, conducted either individually (single interventions) or in combination (combined efforts), with varying timings and durations. Interventions include three low environmental toxicity measures in differing combinations, namely reductions in white-tailed deer (Odocoileus virginianus) populations, broadcast area-application of the entomopathogenic fungus Metarhizium anisopliae, and fipronil-based rodent-targeted bait boxes. To assess the impact of these control efforts, we calibrated a process-based mathematical model to data collected from residential properties in the town of Redding, southwestern Connecticut, where an integrated tick management program to reduce I.xodes scapularis nymphs was conducted from 2013 through 2016. We estimated parameters mechanistically for each of the three treatments, simulated multiple combinations and timings of interventions, and computed the resulting percent reduction of the nymphal peak and of the area under the phenology curve. RESULTS: Simulation outputs suggest that the three-treatment combination and the bait boxes-deer reduction combination had the overall highest impacts on suppressing I. scapularis nymphs. All (single or combined) interventions were more efficacious when implemented for a higher number of years. When implemented for at least 4 years, most interventions (except the single application of the entomopathogenic fungus) were predicted to strongly reduce the nymphal peak compared with the no intervention scenario. Finally, we determined the optimal period to apply the entomopathogenic fungus in residential yards, depending on the number of applications. CONCLUSIONS: Computer simulation is a powerful tool to identify the optimal deployment of individual and combined tick management approaches, which can synergistically contribute to short-to-long-term, costeffective, and sustainable control of tick-borne diseases in integrated tick management (ITM) interventions.


Subject(s)
Deer , Ixodes , Metarhizium , Tick Control , Animals , Ixodes/microbiology , Ixodes/physiology , Tick Control/methods , Metarhizium/pathogenicity , Metarhizium/physiology , Tick Infestations/prevention & control , Tick Infestations/veterinary , Lyme Disease/prevention & control , Lyme Disease/transmission , Connecticut , Models, Theoretical , Pyrazoles , Pest Control, Biological/methods , Nymph , Rodentia , Insecticides
9.
Int J Mol Sci ; 25(15)2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39125945

ABSTRACT

Ticks transmit a variety of pathogens, including rickettsia and viruses, when they feed on blood, afflicting humans and other animals. Bioactive components acting on inflammation, coagulation, and the immune system were reported to facilitate ticks' ability to suck blood and transmit tick-borne diseases. In this study, a novel peptide, IstTx, from an Ixodes scapularis cDNA library was analyzed. The peptide IstTx, obtained by recombinant expression and purification, selectively inhibited a potassium channel, TREK-1, in a dose-dependent manner, with an IC50 of 23.46 ± 0.22 µM. The peptide IstTx exhibited different characteristics from fluoxetine, and the possible interaction of the peptide IstTx binding to the channel was explored by molecular docking. Notably, extracellular acidification raised its inhibitory efficacy on the TREK-1 channel. Our results found that the tick-derived peptide IstTx blocked the TREK-1 channel and provided a novel tool acting on the potassium channel.


Subject(s)
Peptides , Potassium Channels, Tandem Pore Domain , Potassium Channels, Tandem Pore Domain/metabolism , Potassium Channels, Tandem Pore Domain/genetics , Potassium Channels, Tandem Pore Domain/antagonists & inhibitors , Potassium Channels, Tandem Pore Domain/chemistry , Animals , Humans , Peptides/pharmacology , Peptides/chemistry , Peptides/metabolism , Ixodes/metabolism , Molecular Docking Simulation , Amino Acid Sequence , HEK293 Cells , Potassium Channel Blockers/pharmacology , Potassium Channel Blockers/chemistry , Ticks/metabolism
10.
Front Cell Infect Microbiol ; 14: 1450353, 2024.
Article in English | MEDLINE | ID: mdl-39193502

ABSTRACT

Ticks are obligate hematophagous arthropods that transmit a wide range of pathogens to humans as well as wild and domestic animals. They also harbor a non-pathogenic microbiota, although our previous study has shown that the diverse bacterial microbiome in the midgut of Ixodes ricinus is quantitatively poor and lacks a core. In artificial infections by capillary feeding of ticks with two model bacteria (Gram-positive Micrococcus luteus and Gram-negative Pantoea sp.), rapid clearance of these microbes from the midgut was observed, indicating the presence of active immune mechanisms in this organ. In the current study, RNA-seq analysis was performed on the midgut of I. ricinus females inoculated with either M. luteus or Pantoea sp. or with sterile water as a control. While no immune-related transcripts were upregulated by microbial inoculation compared to that of the sterile control, capillary feeding itself triggered dramatic transcriptional changes in the tick midgut. Manual curation of the transcriptome from the midgut of unfed I. ricinus females, complemented by the proteomic analysis, revealed the presence of several constitutively expressed putative antimicrobial peptides (AMPs) that are independent of microbial stimulation and are referred to here as 'guard' AMPs. These included two types of midgut-specific defensins, two different domesticated amidase effector 2 (Dae2), microplusin/ricinusin-related molecules, two lysozymes, and two gamma interferon-inducible lysosomal thiol reductases (GILTs). The in vitro antimicrobial activity assays of two synthetic mature defensins, defensin 1 and defensin 8, confirmed their specificity against Gram-positive bacteria showing exceptional potency to inhibit the growth of M. luteus at nanomolar concentrations. The antimicrobial activity of midgut defensins is likely part of a multicomponent system responsible for the rapid clearance of bacteria in the tick midgut. Further studies are needed to evaluate the role of other identified 'guard' AMPs in controlling microorganisms entering the tick midgut.


Subject(s)
Ixodes , Animals , Ixodes/microbiology , Ixodes/immunology , Female , Micrococcus luteus/immunology , Antimicrobial Peptides/metabolism , Transcriptome , Gastrointestinal Tract/microbiology , Gastrointestinal Tract/immunology , Gene Expression Profiling , Proteomics
11.
Parasitol Res ; 123(8): 306, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39167261

ABSTRACT

The research of the influences of man-made electromagnetic fields on tick physiology has been very sparse and long neglected since the pioneer studies published in 1996 and 2000. Once multiple behavioral tests confirmed an attraction and possible perception of electromagnetic fields in ticks, a new interest in this topic erupted in recent years. In this study, qRT-PCR is utilized to determine the changes in the mRNA transcript levels of neuropeptides SIFamide and myoinhibitory peptide (mip and sifa) and their representative receptors (mip-r1 and sifa-r1) in the synganglia of the tick Ixodes ricinus irradiated by 900 MHz radiofrequency electromagnetic field. It was determined that 40 V/m intensity has a significant suppressory effect on the transcript levels of all genes after at least 60 minutes of constant exposure in both sexes. Commonly occurring intensity of radiation in urban areas (2 V/m) produced an elevation in mRNA levels after various timespans in every gene. A significant decrease of transcript abundances was detected in females after one hour of exposure to 2 V/m. Results of this study widen the knowledge of EMF-induced alterations in the neurophysiology of I. ricinus, the most commonly distributed hard tick in Europe.


Subject(s)
Ixodes , Animals , Ixodes/genetics , Ixodes/radiation effects , Ixodes/physiology , Female , Male , Electromagnetic Radiation , Neuropeptides/genetics , Neuropeptides/metabolism , Electromagnetic Fields , Gene Expression Regulation/radiation effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription, Genetic/radiation effects
12.
J Med Entomol ; 61(5): 1203-1213, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39119633

ABSTRACT

Among approaches aimed at reducing Lyme disease risk in the environment, those targeting reservoirs of Borrelia burgdorferi Johnson are promising because they have the potential to reduce both the density of questing Ixodes scapularis Say (Acari: Ixodidea) ticks and the prevalence of B. burgdorferi in the tick population. In this 4-yr field study, we treated a population of wild small mammals with 2 densities of fluralaner baits and investigated the effect of the treatment on 3 parameters of the endemic cycle of B. burgdorferi: (i) the prevalence of infected Peromyscus mice (PIM), (ii) the density of questing nymphs (DON), and (iii) the prevalence of infected questing nymphs (NIP). We demonstrated that fluralaner baiting is effective at reducing tick infestation of Peromyscus mice, the main reservoir of B. burgdorferi in central and northeastern North America, in the laboratory and the field. Results from this study showed a significant decrease in B. burgdorferi infection in mice (odds ratio: 0.37 [CI95: 0.17 to 0.83]). A reduction in the DON between 45.4% [CI95: 22.4 to 61.6] and 62.7% [CI95: 45.9 to 74.2] occurred in treated area when compared with control areas. No significant effect was reported on the NIP. These results confirm the hypothesis that fluralaner baits have an effect on B. burgdorferi endemic cycle, with the potential to reduce the density of B. burgdorferi-infected ticks in the environment. Further studies performed in various habitats and public health intervention contexts are needed to refine and operationalize this approach for reducing Lyme disease risk in the environment.


Subject(s)
Borrelia burgdorferi , Isoxazoles , Ixodes , Lyme Disease , Peromyscus , Animals , Isoxazoles/administration & dosage , Ixodes/microbiology , Ixodes/growth & development , Lyme Disease/transmission , Lyme Disease/prevention & control , Lyme Disease/epidemiology , Peromyscus/parasitology , Nymph/growth & development , Nymph/microbiology , Acaricides
13.
mBio ; 15(9): e0174924, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39145656

ABSTRACT

Lyme disease, caused by spirochetes in the Borrelia burgdorferi sensu lato clade within the Borrelia genus, is transmitted by Ixodes ticks and is currently the most prevalent and rapidly expanding tick-borne disease in Europe and North America. We report complete genome sequences of 47 isolates that encompass all established species in this clade while highlighting the diversity of the widespread human pathogenic species B. burgdorferi. A similar set of plasmids has been maintained throughout Borrelia divergence, indicating that they are a key adaptive feature of this genus. Phylogenetic reconstruction of all sequenced Borrelia genomes revealed the original divergence of Eurasian and North American lineages and subsequent dispersals that introduced B. garinii, B. bavariensis, B. lusitaniae, B. valaisiana, and B. afzelii from East Asia to Europe and B. burgdorferi and B. finlandensis from North America to Europe. Molecular phylogenies of the universally present core replicons (chromosome and cp26 and lp54 plasmids) are highly consistent, revealing a strong clonal structure. Nonetheless, numerous inconsistencies between the genome and gene phylogenies indicate species dispersal, genetic exchanges, and rapid sequence evolution at plasmid-borne loci, including key host-interacting lipoprotein genes. While localized recombination occurs uniformly on the main chromosome at a rate comparable to mutation, lipoprotein-encoding loci are recombination hotspots on the plasmids, suggesting adaptive maintenance of recombinant alleles at loci directly interacting with the host. We conclude that within- and between-species recombination facilitates adaptive sequence evolution of host-interacting lipoprotein loci and contributes to human virulence despite a genome-wide clonal structure of its natural populations. IMPORTANCE: Lyme disease (also called Lyme borreliosis in Europe), a condition caused by spirochete bacteria of the genus Borrelia, transmitted by hard-bodied Ixodes ticks, is currently the most prevalent and rapidly expanding tick-borne disease in the United States and Europe. Borrelia interspecies and intraspecies genome comparisons of Lyme disease-related bacteria are essential to reconstruct their evolutionary origins, track epidemiological spread, identify molecular mechanisms of human pathogenicity, and design molecular and ecological approaches to disease prevention, diagnosis, and treatment. These Lyme disease-associated bacteria harbor complex genomes that encode many genes that do not have homologs in other organisms and are distributed across multiple linear and circular plasmids. The functional significance of most of the plasmid-borne genes and the multipartite genome organization itself remains unknown. Here we sequenced, assembled, and analyzed whole genomes of 47 Borrelia isolates from around the world, including multiple isolates of the human pathogenic species. Our analysis elucidates the evolutionary origins, historical migration, and sources of genomic variability of these clinically important pathogens. We have developed web-based software tools (BorreliaBase.org) to facilitate dissemination and continued comparative analysis of Borrelia genomes to identify determinants of human pathogenicity.


Subject(s)
Genome, Bacterial , Lipoproteins , Lyme Disease , Phylogeny , Recombination, Genetic , Selection, Genetic , Lyme Disease/microbiology , Lyme Disease/transmission , Lipoproteins/genetics , Humans , North America , Genetic Variation , Borrelia burgdorferi/genetics , Borrelia burgdorferi/classification , Europe , Plasmids/genetics , Ixodes/microbiology , Borrelia/genetics , Borrelia/classification , Evolution, Molecular , Whole Genome Sequencing , Animals , Host Microbial Interactions/genetics , Borrelia burgdorferi Group/genetics , Borrelia burgdorferi Group/classification
14.
J Virol ; 98(8): e0056024, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39087762

ABSTRACT

Powassan virus (POWV) is an emergent tick-borne flavivirus that causes fatal encephalitis in the elderly and long-term neurologic sequelae in survivors. How age contributes to severe POWV encephalitis remains an enigma, and no animal models have assessed age-dependent POWV neuropathology. Inoculating C57BL/6 mice with a POWV strain (LI9) currently circulating in Ixodes ticks resulted in age-dependent POWV lethality 10-20 dpi. POWV infection of 50-week-old mice was 82% fatal with lethality sequentially reduced by age to 7.1% in 10-week-old mice. POWV LI9 was neuroinvasive in mice of all ages, causing acute spongiform CNS pathology and reactive gliosis 5-15 dpi that persisted in survivors 30 dpi. High CNS viral loads were found in all mice 10 dpi. However, by 15 dpi, viral loads decreased by 2-4 logs in 10- to 40-week-old mice, while remaining at high levels in 50-week-old mice. Age-dependent differences in CNS viral loads 15 dpi occurred concomitantly with striking changes in CNS cytokine responses. In the CNS of 50-week-old mice, POWV induced Th1-type cytokines (IFNγ, IL-2, IL-12, IL-4, TNFα, IL-6), suggesting a neurodegenerative pro-inflammatory M1 microglial program. By contrast, in 10-week-old mice, POWV-induced Th2-type cytokines (IL-10, TGFß, IL-4) were consistent with a neuroprotective M2 microglial phenotype. These findings correlate age-dependent CNS cytokine responses and viral loads with POWV lethality and suggest potential neuroinflammatory therapeutic targets. Our results establish the age-dependent lethality of POWV in a murine model that mirrors human POWV severity and long-term CNS pathology in the elderly. IMPORTANCE: Powassan virus is an emerging tick-borne flavivirus causing lethal encephalitis in aged individuals. We reveal an age-dependent POWV murine model that mirrors human POWV encephalitis and long-term CNS damage in the elderly. We found that POWV is neuroinvasive and directs reactive gliosis in all age mice, but at acute stages selectively induces pro-inflammatory Th1 cytokine responses in 50-week-old mice and neuroprotective Th2 cytokine responses in 10-week-old mice. Our findings associate CNS viral loads and divergent cytokine responses with age-dependent POWV lethality and survival outcomes. Responses of young mice suggest potential therapeutic targets and approaches for preventing severe POWV encephalitis that may be broadly applicable to other neurodegenerative diseases. Our age-dependent murine POWV model permits analysis of vaccines that prevent POWV lethality, and therapeutics that resolve severe POWV encephalitis.


Subject(s)
Cytokines , Disease Models, Animal , Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Mice, Inbred C57BL , Neuroglia , Viral Load , Animals , Mice , Encephalitis Viruses, Tick-Borne/immunology , Encephalitis, Tick-Borne/immunology , Encephalitis, Tick-Borne/virology , Encephalitis, Tick-Borne/mortality , Encephalitis, Tick-Borne/pathology , Cytokines/metabolism , Cytokines/immunology , Neuroglia/virology , Neuroglia/immunology , Neuroglia/pathology , Female , Age Factors , Ixodes/virology , Ixodes/immunology , Central Nervous System/virology , Central Nervous System/immunology , Central Nervous System/pathology , Brain/virology , Brain/pathology , Brain/immunology
15.
J R Soc Interface ; 21(217): 20240004, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39106949

ABSTRACT

Mechanistic mathematical models such as ordinary differential equations (ODEs) have a long history for their use in describing population dynamics and determining estimates of key parameters that summarize the potential growth or decline of a population over time. More recently, geographic information systems (GIS) have become important tools to provide a visual representation of statistically determined parameters and environmental features over space. Here, we combine these tools to form a 'GIS-ODE' approach to generate spatiotemporal maps predicting how projected changes in thermal climate may affect population densities and, uniquely, population dynamics of Ixodes ricinus, an important tick vector of several human pathogens. Assuming habitat and host densities are not greatly affected by climate warming, the GIS-ODE model predicted that, even under the lowest projected temperature increase, I. ricinus nymph densities could increase by 26-99% in Scotland, depending on the habitat and climate of the location. Our GIS-ODE model provides the vector-borne disease research community with a framework option to produce predictive, spatially explicit risk maps based on a mechanistic understanding of vector and vector-borne disease transmission dynamics.


Subject(s)
Climate Change , Geographic Information Systems , Ixodes , Models, Biological , Animals , Scotland , Ixodes/physiology , Population Dynamics , Humans , Ecosystem
16.
PLoS One ; 19(8): e0309367, 2024.
Article in English | MEDLINE | ID: mdl-39190767

ABSTRACT

In order to predict the global potential distribution range of Ixodes pacificus (I. pacificus) under different climate scenario models in the future, analyze the major climate factors affecting its distribution, and provide references for the transformation of passive vector surveillance into active vector surveillance, the maximum entropy model (MaxEnt) was used in this study to estimate the global potential distribution range of I. pacificus under historical climate scenarios and different future climate scenarios. The global distribution data of I. pacificus were screened by ENMtools and ArcGIS 10.8 software, and a total of 563 distribution data of I. pacificus were obtained. Maxent 3.4.1 and R 4.0.3 were used to screen climate variables according to the contribution rate of environmental variables, knife cutting method and correlation analysis of variables. R 4.0.3 was used to calculate model regulation frequency doubling and feature combination to adjust MaxEnt parameters. The model results showed that the training omission rate was in good agreement with the theoretical omission rate, and the area under ROC curve (AUC) value of the model was 0.978. Among the included environmental variables, the Tmin2 (minimum temperature in February) and Prec1 (precipitation in January) contributed the most to the model, providing more effective information for the distribution of I. pacificus. MaxEnt model revealed that the distribution range of I. pacificus was dynamically changing. The main potential suitable areas are distributed in North America, South America, Europe, Oceania and Asia. Under the future climate scenario model, the potential suitable areas show a downward trend, but the countries and regions ieeeeeeenvolved in the suitable areas do not change much. Therefore, the invasion risk of the potential suitable area of I. pacificus should be paid attention to.


Subject(s)
Climate Change , Ixodes , Animals , Ixodes/physiology , Animal Distribution , Temperature
17.
Emerg Infect Dis ; 30(9): 1934-1938, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39174031

ABSTRACT

Severe babesiosis with 9.8% parasitemia was diagnosed in a patient in the Netherlands who had previously undergone splenectomy. We confirmed Babesia venatorum using PCR and sequencing. B. venatorum was also the most prevalent species in Ixodes ricinus ticks collected around the patient's home. Our findings warrant awareness for severe babesiosis in similar patients.


Subject(s)
Babesia , Babesiosis , Babesiosis/diagnosis , Babesiosis/parasitology , Babesia/genetics , Babesia/isolation & purification , Babesia/classification , Humans , Netherlands , Animals , Male , Splenectomy , Middle Aged , Ixodes/parasitology
18.
Parasit Vectors ; 17(1): 345, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160635

ABSTRACT

BACKGROUND: Bartonella spp. infect a variety of vertebrates throughout the world, with generally high prevalence. Several Bartonella spp. are known to cause diverse clinical manifestations in humans and have been recognized as emerging pathogens. These bacteria are mainly transmitted by blood-sucking arthropods, such as fleas and lice. The role of ticks in the transmission of Bartonella spp. is unclear. METHODS: A recently developed quadruplex polymerase chain reaction (PCR) amplicon next-generation sequencing approach that targets Bartonella-specific fragments on gltA, ssrA, rpoB, and groEL was applied to test host-seeking Ixodes scapularis ticks (n = 1641; consisting of 886 nymphs and 755 adults) collected in 23 states of the eastern half of the United States and Ixodes pacificus ticks (n = 966; all nymphs) collected in California in the western United States for the presence of Bartonella DNA. These species were selected because they are common human biters and serve as vectors of pathogens causing the greatest number of vector-borne diseases in the United States. RESULTS: No Bartonella DNA was detected in any of the ticks tested by any target. CONCLUSIONS: Owing to the lack of Bartonella detection in a large number of host-seeking Ixodes spp. ticks tested across a broad geographical region, our results strongly suggest that I. scapularis and I. pacificus are unlikely to contribute more than minimally, if at all, to the transmission of Bartonella spp.


Subject(s)
Bartonella Infections , Bartonella , Ixodes , Animals , Ixodes/microbiology , Bartonella/genetics , Bartonella/isolation & purification , United States/epidemiology , Bartonella Infections/transmission , Bartonella Infections/epidemiology , Bartonella Infections/microbiology , Nymph/microbiology , Polymerase Chain Reaction , DNA, Bacterial/genetics , Humans , Female , High-Throughput Nucleotide Sequencing
19.
PeerJ ; 12: e17944, 2024.
Article in English | MEDLINE | ID: mdl-39193518

ABSTRACT

Environmental dimensions, such as temperature, precipitation, humidity, and vegetation type, influence the activity, survival, and geographic distribution of tick species. Ticks are vectors of various pathogens that cause disease in humans, and Ixodes scapularis and Amblyomma americanum are among the tick species that transmit pathogens to humans across the central and eastern United States. Although their potential geographic distributions have been assessed broadly via ecological niche modeling, no comprehensive study has compared ecological niche signals between ticks and tick-borne pathogens. We took advantage of National Ecological Observatory Network (NEON) data for these two tick species and associated bacteria pathogens across North America. We used two novel statistical tests that consider sampling and absence data explicitly to perform these explorations: a univariate analysis based on randomization and resampling, and a permutational multivariate analysis of variance. Based on univariate analyses, in Amblyomma americanum, three pathogens (Borrelia lonestari, Ehrlichia chaffeensis, and E. ewingii) were tested; pathogens showed nonrandom distribution in at least one environmental dimension. Based on the PERMANOVA test, the null hypothesis that the environmental position and variation of pathogen-positive samples are equivalent to those of A. americanum could not be rejected for any of the pathogens, except for the pathogen E. ewingii in maximum and minimum vapor pressure and minimum temperature. For Ixodes scapularis, six pathogens (A. phagocytophilum, Babesia microti, Borrelia burgdorferi sensu lato, B. mayonii, B. miyamotoi, and Ehrlichia muris-like) were tested; only B. miyamotoi was not distinct from null expectations in all environmental dimensions, based on univariate tests. In the PERMANOVA analyses, the pathogens departed from null expectations for B. microti and B. burgdorferi sensu lato, with smaller niches in B. microti, and larger niches in B. burgdorferi sensu lato, than the vector. More generally, this study shows the value of large-scale data resources with consistent sampling methods, and known absences of key pathogens in particular samples, for answering public health questions, such as the relationship of presence and absence of pathogens in their hosts respect to environmental conditions.


Subject(s)
Amblyomma , Ixodes , Animals , Ixodes/microbiology , Amblyomma/microbiology , North America , Borrelia/isolation & purification , Borrelia/genetics , Borrelia/pathogenicity , Ecosystem , Ehrlichia/isolation & purification , Ehrlichia/genetics , Ehrlichia chaffeensis/genetics , Arachnid Vectors/microbiology , Humans , Tick-Borne Diseases/transmission , Tick-Borne Diseases/microbiology , Tick-Borne Diseases/epidemiology
20.
Emerg Microbes Infect ; 13(1): 2384472, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39042034

ABSTRACT

We detected 24 Encephalitozoon cuniculi positive Ixodes ricinus ticks of 284 collected in the Czech Republic. Since the route of transmission of microsporidia is not fully understood, the presence of microsporidia in ticks raises the question of whether they may be involved in the transmission of these pathogens.


Subject(s)
Ixodes , Animals , Humans , Czech Republic , Ixodes/microbiology , Tick-Borne Diseases/transmission , Tick-Borne Diseases/microbiology , Microsporidiosis/transmission , Encephalitozoon cuniculi/isolation & purification , Encephalitozoon cuniculi/genetics , Encephalitozoonosis/transmission , Encephalitozoonosis/microbiology
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